7UYF

Human PRMT5:MEP50 structure with Fragment 4 and MTA Bound

7UYF の概要

• エントリーDOI: 10.2210/pdb7uyf/pdb
• 分子名称: Protein arginine N-methyltransferase 5, Methylosome protein 50, 4-methyl-1,5-naphthyridin-2-amine, ... (7 entities in total)
• 機能のキーワード: mtap, methyl transferase, fragment-based lead discovery, fbdd, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 112507.27

構造登録者

Gunn, R.J.,Lawson, J.D.,Smith, C.R. (登録日: 2022-05-06, 公開日: 2022-10-05, 最終更新日: 2024-05-22)

主引用文献

Smith, C.R.,Kulyk, S.,Ahmad, M.U.D.,Arkhipova, V.,Christensen, J.G.,Gunn, R.J.,Ivetac, A.,Ketcham, J.M.,Kuehler, J.,Lawson, J.D.,Thomas, N.C.,Wang, X.,Marx, M.A.
Fragment optimization and elaboration strategies - the discovery of two lead series of PRMT5/MTA inhibitors from five fragment hits.
Rsc Med Chem, 13:1549-1564, 2022

PubMed Abstract: Here we describe the early stages of a fragment-based lead discovery (FBLD) project for a recently elucidated synthetic lethal target, the PRMT5/MTA complex, for the treatment of -deleted cancers. Starting with five fragment/PRMT5/MTA X-ray co-crystal structures, we employed a two-phase fragment elaboration process encompassing optimization of fragment hits and subsequent fragment growth to increase potency, assess synthetic tractability, and enable structure-based drug design. Two lead series were identified, one of which led to the discovery of the clinical candidate MRTX1719.

PubMed: 36545438
DOI: 10.1039/d2md00163b

実験手法

X-RAY DIFFRACTION (2.82 Å)